The Therapeutic Potential of Common Herbal and Nano-Based Herbal Formulations against Ovarian Cancer: New Insight into the Current Evidence

Ovarian cancer (OCa) is characterized as one of the common reasons for cancer-associated death in women globally. This gynecological disorder is chiefly named the “silent killer” due to lacking an association between disease manifestations in the early stages and OCa. Because of the disease recurrence and resistance to common therapies, discovering an effective therapeutic way against the disease is a challenge. According to documents, some popular herbal formulations, such as curcumin, quercetin, and resveratrol, can serve as an anti-cancer agent through different mechanisms. However, these herbal products may be accompanied by some pharmacological limitations, such as poor bioavailability, instability, and weak water solubility. On the contrary, using nano-based material, e.g., nanoparticles (NPs), micelles, liposomes, can significantly solve these limitations. Therefore, in the present study, we will summarize the anti-cancer aspects of these herbal and-nano-based herbal formulations with a focus on their mechanisms against OCa.

Applying Machine Learning Algorithms to Predict Endometriosis Onset

Endometriosis is a commonly occurring progressive gynecological disorder, in which tissues similar to the lining of the uterus grow on other parts of the female body, including ovaries, fallopian tubes, and bowel. It is one of the primary causes of pelvic discomfort and fertility challenges in women. The actual cause of the endometriosis is still undetermined. As a result, the objective of the chapter is to identify the drivers of endometriosis’ diagnoses via leveraging selected advanced machine learning (ML) algorithms. The primary risks of infertility and other health complications can be minimized to a greater extent if a likelihood of endometriosis could be predicted well in advance. Logistic regression (LR) and eXtreme Gradient Boosting (XGB) algorithms leveraged 36 months of medical history data to demonstrate the feasibility. Several direct and indirect features were identified as important to an accurate prediction of the condition onset, including selected diagnosis and procedure codes. Creating analytical tools based on the model results that could be integrated into the Electronic Health Records (EHR) systems and easily accessed by healthcare providers might aid the objective of improving the diagnostic processes and result in a timely and precise diagnosis, ultimately increasing patient care and quality of life.

Acupuncture for adenomyosis: a systematic review and meta-analysis

Review question / Objective: Can patients with adenomyosis benefit from acupuncture treatments? Evaluation of current evidence with respect to the efficacy and safety of acupuncture for adenomyosis by conducting a systematic review and meta-analysis of the available randomized controlled trial. Condition being studied: Adenomyosis is a gynecological disorder defined as the presence of the endometrial gland and stroma cells within the myometrium. This condition mainly occurs in women who are multiparous and over the age of 30. Among women undergoing hysterectomy, the frequency of adenomyosis is reported to range from 8.8% to 61.5%. Adenomyosis is also observed in 20. 9% to 34% of women who have been referred for pelvic imaging. The incidence of adenomyosis in the general population remains uncertain. Adenomyosis can significantly decrease the patient’s quality of life, with the clinical presentations of menorrhagia, dysmenorrhea, metrorrhagia, chronic pelvic pain and dyspareunia.

Efficacy and Safety of Acupuncture Vs. Hormone Therapy for Menopausal Syndrome: A Systematic Review and Meta-Analysis

Menopausal syndrome (MPS) is a common gynecological disorder around the time of menopause, and hormone therapy (HT) is the first-line treatment for it. However, HT is prone to cause adverse reactions in MPS patients treated with HT. Acupuncture is a popular non-pharmaceutical therapy for MPS, but the differences in the efficacy and safety between acupuncture and HT remain unclear. The purpose of this evidence-based study is to address this issue. Five databases were searched for potentially eligible RCTs. All RCTs comparing acupuncture with HT in the treatment of MPS were included in this study. The clinical effective rate was the primary outcome. Kupperman index, serum follicle-stimulating hormone (FSH), luteinizing hormone (LH), estradiol (E[Formula: see text], and side effects were the secondary outcomes. A total of 15 RCTs recruiting 1376 MPS patients were included. Results of meta-analysis showed that compared with HT, acupuncture significantly improved clinical effective rate (RR = 1.09, 95% CI 1.03 to 1.16, [Formula: see text] = 0.005), decreased the Kupperman index (WMD = −2.55, 95% CI = −2.93 to −2.17, [Formula: see text] < 0.00001) and the incidence of side effects (RR = 0.14, 95% CI = 0.06–0.32, [Formula: see text] < 0.00001). There were no statistically significant differences in serum FSH (WMD = −1.36, 95% CI = −3.25–0.53, [Formula: see text] = 0.16), E2(WMD = −1.11, 95% CI = −2.59–0.37, [Formula: see text] = 0.14), or LH (WMD = −1.87, 95% CI = −4.58–0.83, [Formula: see text] = 0.17) between the acupuncture and HT groups. Based on the current evidence, manual acupuncture is safer and more effective than HT and is recommended for the treatment of MPS, but the evidence for the efficacy of other types of acupuncture is inconclusive.

The Role of Long Non-Coding RNAs in Endometriosis

Endometriosis is a chronic gynecological disorder affecting the quality of life and fertility of many women around the world. Heterogeneous and non-specific symptoms may lead to a delay in diagnosis, with treatment options limited to surgery and hormonal therapy. Hence, there is a need to better understand the pathogenesis of the disease to improve diagnosis and treatment. Long non-coding RNAs (lncRNAs) have been increasingly shown to be involved in gene regulation but remain relatively under investigated in endometriosis. Mutational and transcriptomic studies have implicated lncRNAs in the pathogenesis of endometriosis. Single-nucleotide polymorphisms (SNPs) in lncRNAs or their regulatory regions have been associated with endometriosis. Genome-wide transcriptomic studies have identified lncRNAs that show deregulated expression in endometriosis, some of which have been subjected to further experiments, which support a role in endometriosis. Mechanistic studies indicate that lncRNAs may regulate genes involved in endometriosis by acting as a molecular sponge for miRNAs, by directly targeting regulatory elements via interactions with chromatin or transcription factors or by affecting signaling pathways. Future studies should concentrate on determining the role of uncharacterized lncRNAs revealed by endometriosis transcriptome studies and the relevance of lncRNAs implicated in the disease by in vitro and animal model studies.

The Role of Peritoneal Macrophages in Endometriosis

Endometriosis is an estrogen-dependent gynecological disorder, defined as the growth of endometrial stromal cells and glands at extrauterine sites. Endometriotic lesions are more frequently located into the abdominal cavity, although they can also be implanted in distant places. Among its etiological factors, the presence of immune dysregulation occupies a prominent place, pointing out the beneficial and harmful outcomes of macrophages in the pathogenesis of this disease. Macrophages are tissue-resident cells that connect innate and adaptive immunity, playing a key role in maintaining local homeostasis in healthy conditions and being critical in the development and sustainment of many inflammatory diseases. Macrophages accumulate in the peritoneal cavity of women with endometriosis, but their ability to clear migrated endometrial fragments seems to be inefficient. Hence, the characteristics of the peritoneal immune system in endometriosis must be further studied to facilitate the search for new diagnostic and therapeutic tools. In this review, we summarize recent relevant advances obtained in both mouse, as the main animal model used to study endometriosis, and human, focusing on peritoneal macrophages obtained from endometriotic patients and healthy donors, under the perspective of its future clinical translation to the role that these cells play on this pathology.

Development and evaluation of Pharmacosome formulations of Mefenamic acid

Patience who suffered from menstrual pain disease is generally prescribed the non-steroidal anti-inflammatory drug (NSAIDs). Monorrhagia or another blood disorder & some gynecological disorder, which impairs body function and acts as an economic burden. Due to respective use of ACE by oral route, it may cause GI complication such as bleeding, pain, perforation, abdominal pain, and swelling. To decrease the side effect of ACE, it is given by topical route in promotes the safety & efficacy of the ACE. The Mefenamic Acid pharmacosomes were prepared by the hand shaking method technique and evaluated by various methods such as in-vitro release study, % yield, drug entrapment efficiency, pH of the prepared formulation. The prepared system was also characterized by FTIR spectrophotometer to identify the drug-excipients interaction. The maximum entrapment efficiency of pharmacosomes was found to be 90%. The main aim of this study was to develop and characterized a vesicular drug carrier system for topical delivery of Mefenamic Acid to overcome the problem related with oral route.

Endometriotic Peritoneal Fluid Stimulates Recruitment of CD4+CD25highFOXP3+ Treg Cells

Endometriosis is a common gynecological disorder characterized by the presence of endometrial-like tissue outside the uterus. The disease is associated with disturbed local and systemic immunity. It has been reported that the proportion of CD4+CD25highFOXP3+ Treg cells may be significantly increased in the peritoneal fluid of patients with endometriosis. Therefore, the aim of our study was to investigate whether the proportions of Treg cells in the peritoneal cavity of patients with endometriosis are related to the chemotactic and stimulatory activity of the local peritoneal milieu. The peritoneal fluid was collected from 13 women with ovarian endometriosis and 12 control women without the disease. T cell populations were analyzed by flow cytometry, cytokines and chemokines were evaluated using the cytometric bead kit, and cell chemotaxis was studied by cell migration assay. We confirmed that the proportions of Treg cells are increased in the peritoneal fluid of women with endometriosis as compared to the control women. Endometriosis was also associated with elevated concentrations of IL-6, IL-10, and TGF-β1/2 as well as CCL20, CXCL8, CXCL9, and CXCL10. We did not reveal any changes in the proportion of peritoneal Th17 cells and concentrations of IL-17A. Peritoneal Treg cells positively correlated with concentrations of TGF-β, IL-10, and CCL20. Endometriotic peritoneal fluid stimulated chemotaxis of both CD4+ and Treg cells. This chemotactic activity positively correlated with concentrations of CCL20. CCL20 stimulated the migration of Treg cells, and the chemotactic activity of the endometriotic peritoneal fluid was inhibited by neutralizing anti-CCL20 antibodies. These results imply that increased proportions of the peritoneal Treg cells in women with endometriosis may result from attraction and activation by local chemokines and cytokines, especially CCL20 and TGF-β. Since Treg cells contribute to the immunopathogenesis of endometriosis, their chemotaxis and activation may be considered as a target for therapeutic intervention.

Molecular and Clinical Insights on the Complex Interaction between Oxidative Stress, Apoptosis, and Endobiota in the Pathogenesis of Endometriosis

Endometriosis (EMS) remains, to date, an intriguing and debilitating gynecological disorder that possesses a multifactorial substrate. Recent studies with the objective of elucidating its etiology highlighted the antagonistic effect of EMS on a multiple of processes involved in homeostasis. Although the current oxidative biomarkers clearly reveal the consequences induced by EMS, its implication in the associated inflammatory reactions could be much more complex. Besides the overproduction of reactive oxygen species (ROS) that leads to an exacerbated oxidative response, it also changes the normal expression of several pro-inflammatory modulators, reflected by the fluctuating activity of several pro- and anti-apoptotic mediators whose expression is impaired. In light of this topic, several studies elucidate the involvement of apoptosis in EMS, being brought controversial findings, even reports with no significant change. Further, some authors reported an abnormal expression of multiple genes that are crucial for the overall functionality of the female reproductive system. Cumulatively, it seems that the subsequent oxidative imbalance and apoptosis process impairment could further disrupt the normal removal of unnecessary biological products. Based on all gathered evidence, we could argue that the related stress state could determine human endobiota impairment, which could further participate in the inflammatory and main antioxidant enzyme changes occurring in EMS. Moreover, a correlation between endobiota integrity, inflammation, and oxidative stress (OS) was suggested in relation to the possible predisposition to pathogen determined infections.

M1 Macrophage-Derived Nanovesicles Repolarize M2 Macrophages for Inhibiting the Development of Endometriosis

BackgroundEndometriosis is a common nonmalignant gynecological disorder that affects 10–15% women of reproductive age and causes several symptoms that result in decreased quality of life and a huge social burden. In recent decades, extracellular vesicles (EVs) have gained attention as a potential therapeutic tool; however, the therapeutic effects of EVs against endometriosis have not been reported. Accordingly, in this study, we investigated the feasibility of nanovesicles (NVs) derived from M1 macrophages (M1NVs) in treating endometriosis.MethodsM1NVs were prepared by serial extrusion. Co-culture assays were performed to investigate changes in tube formation and migration/invasion of eutopic endometrial stroma cells (ESCs) obtained from patients with endometriosis (EM-ESCs). A mouse model of endometriosis was established, and mice were treated with phosphate-buffered saline, M0NVs, or M1NVs to evaluate the efficacy and safety of M1NV for treating endometriosis.ResultsM1NVs directly or indirectly inhibited the migration and invasion of EM-ESCs and reduced tube formation. In the mouse model, M1NVs suppressed the development of endometriosis through reprogramming of M2 macrophages, without causing damage to the organs.ConclusionsM1NVs inhibit the development of endometriosis directly, or through repolarizing macrophages from M2 to M1 phenotype. Hence, administration of M1NVs may represent a novel method for the treatment of endometriosis.